Insulin-Ameliorated Peripheral Motor Neuropathy in Spontaneously Diabetic WBN/Kob Rats

Ozaki, Kiyokazu; Yamano, Shotaro; Matsuura, Tetsuro; Narama, Isao

doi:10.1292/jvms.13-0184

Cited by 21 publications

(34 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increasing research studies have supported that diabetes induced neuroinflammation plays a crucial role in tau and Aβ pathogenesis 12,18,19. Whether such neuroprotective effects of minocycline on diabetic metabolism disorder are through inhibiting inflammation is still unclear.…”

Section: Resultsmentioning

confidence: 99%

“…Diabetic models will be successfully established, which occurred with cataract, hyperglycemia, uric acid, diabetic nephropathy, and a blood glucose level equal to or above 150 mg/dL were identified as diabetic while the blood glucose level of normal rats varied between 50 to 135 mg/dL 18,19. Diabetic animals were continually given a high fat and high sugar diet.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Minocycline alleviates beta-amyloid protein and tau pathology via restraining neuroinflammation induced by diabetic metabolic disorder

Cai¹,

Yan²,

Wang³

2013

CIA

View full text Add to dashboard Cite

BackgroundCompelling evidence has shown that diabetic metabolic disorder plays a critical role in the pathogenesis of Alzheimer’s disease, including increased expression of β-amyloid protein (Aβ) and tau protein. Evidence has supported that minocycline, a tetracycline derivative, protects against neuroinflammation induced by neurodegenerative disorders or cerebral ischemia. This study has evaluated minocycline influence on expression of Aβ protein, tau phosphorylation, and inflammatory cytokines (interleukin-1β and tumor necrosis factor-α) in the brain of diabetic rats to clarify neuroprotection by minocycline under diabetic metabolic disorder.MethodAn animal model of diabetes was established by high fat diet and intraperitoneal injection of streptozocin. In this study, we investigated the effect of minocycline on expression of Aβ protein, tau phosphorylation, and inflammatory cytokines (interleukin-1β and tumor necrosis factor-α) in the hippocampus of diabetic rats via immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay.ResultsThese results showed that minocycline decreased expression of Aβ protein and lowered the phosphorylation of tau protein, and retarded the proinflammatory cytokines, but not amyloid precursor protein.ConclusionOn the basis of the finding that minocycline had no influence on amyloid precursor protein and beta-site amyloid precursor protein cleaving enzyme 1 which determines the speed of Aβ generation, the decreases in Aβ production and tau hyperphosphorylation by minocycline are through inhibiting neuroinflammation, which contributes to Aβ production and tau hyperphosphorylation. Minocycline may also lower the self-perpetuating cycle between neuroinflammation and the pathogenesis of tau and Aβ to act as a neuroprotector. Therefore, the ability of minocycline to modulate inflammatory reactions may be of great importance in the selection of neuroprotective agents, especially in chronic conditions like diabetes and Alzheimer’s disease.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Minocycline alleviates beta-amyloid protein and tau pathology via restraining neuroinflammation induced by diabetic metabolic disorder

Cai¹,

Yan²,

Wang³

2013

CIA

View full text Add to dashboard Cite

show abstract

“…off-target effects of insulin. In one study, rats were treated with insulin and severe peripheral neuropathy was noted only in those rats with serum glucose concentrations less than 50 mg/dl, substantiating the on-target (hypoglycemiarelated) effect (Ozaki et al 2010).…”

Section: Can the Animal Model Of Disease Help To Differentiate Betweementioning

confidence: 86%

Use of Animal Models of Human Disease for Nonclinical Safety Assessment of Novel Pharmaceuticals

et al. 2012

View full text Add to dashboard Cite

Animal models of human disease are commonly utilized to gain insight into the potential efficacy and mode of action of novel pharmaceuticals. However, conventional (healthy) rodent and nonrodent models are generally utilized in nonclinical safety testing. Animal models of human disease may be helpful in understanding safety risks of compounds in nonclinical or clinical development, with their greatest value being in targeted or hypothesis-driven studies to help understand the mechanism of a particular toxicity. Limitations of animal models of disease in nonclinical safety testing include a lack of historical control, heterogeneity in disease expression, a limited life span, and confounding effects of the disease. In most instances, animal models of human disease should not be utilized to supplant testing in conventional animal models. While of potential benefit, testing in an animal model of human disease should only be taken after adequate consideration of relevance along with benefits and limitations of the proposed model.

show abstract

“…In rats with experimental diabetes, insulin treatment partially restores resting NBF, 4,22 improves vasa nervorum reactivity 23 and enhances nerve function. 4,[24][25][26] How insulin treatment impacts microangiopathy remains unclear, [26][27][28] and whether it alters the relationship between blood pressure and NBF is unknown.…”

Section: Introductionmentioning

confidence: 99%

The relationship between blood pressure and sciatic nerve blood flow velocity in rats with insulin-treated experimental diabetes

Olver

Grisé

McDonald

et al. 2014

Diabetes and Vascular Disease Research

View full text Add to dashboard Cite

Peripheral nerve blood flow (NBF) does not autoregulate but, instead, responds passively to changes in mean arterial pressure (MAP). How this relationship is impacted by insulin-treated experimental diabetes (ITED) is unknown. We tested the hypothesis that ITED will reduce NBF across a range of MAP in Sprague Dawley rats. Following 10 weeks of control or ITED conditions, conscious MAP (tail-cuff) was measured, and under anaesthesia, the MAP (carotid artery catheter, pressure transducer) and NBF (Doppler ultrasound, 40 MHz) responses to sodium nitroprusside (60 µg/kg) and phenylephrine (12 µg/kg) infusion were recorded (regression equations for MAP vs NBF were created for each rodent). Thereafter, motor nerve conduction velocity (MNCV) and nerve vascularization (haematoxylin and eosin stain) were determined. Conscious MAP was higher and MNCV was lower in the ITED group (p < 0.01). In response to drug infusions, the ΔMAP and ΔNBF were similar between groups (p ≥ 0.18). Estimated conscious NBF (based on substituting conscious MAP values into each individual regression equation) was greater in the ITED group (p < 0.01). Sciatic nerve vascularization was similar between groups (p ≥ 0.50). In contrast to the hypothesis, NBF was not reduced across a range of MAP. In spite of increased estimated conscious NBF values, MNCV was reduced in rats with ITED.

show abstract

Insulin-Ameliorated Peripheral Motor Neuropathy in Spontaneously Diabetic WBN/Kob Rats

Cited by 21 publications

References 23 publications

Minocycline alleviates beta-amyloid protein and tau pathology via restraining neuroinflammation induced by diabetic metabolic disorder

Minocycline alleviates beta-amyloid protein and tau pathology via restraining neuroinflammation induced by diabetic metabolic disorder

Use of Animal Models of Human Disease for Nonclinical Safety Assessment of Novel Pharmaceuticals

The relationship between blood pressure and sciatic nerve blood flow velocity in rats with insulin-treated experimental diabetes

Contact Info

Product

Resources

About